Label-free photonic biosensors can be used for performing sensitive and quantitative multiparameter measurements on biological systems and can therefore contribute to major advances in medical analyses, food quality control, drug development and environmental monitoring. Additionally they offer the prospect of being incorporated in laboratories-on-a-chip that are capable of doing measurements at the point-of-care at an affordable cost.
A crucial component in most of these photonic biosensors is a transducer that can transform a refractive index change in its environment to a measurable change in an optical signal, e.g. an optical transmission signal. Silicon-on-insulator may be a material system with many assets for such transducers. First, it has a high refractive index contrast permitting very compact sensors of which many can be incorporated on a single chip, enabling multiplexed sensing. Second, silicon-on-insulator photonic chips can be made with CMOS-compatible process steps, allowing for a strong reduction of the chip cost for high volume fabrication. These sensor chips can therefore be disposable, meaning that the chip is only used once, avoiding complex cleaning of the sensor surface after use. Typically, a spectral shift of the transmission spectrum of the transducer is used to quantify the measured refractive index change. This method can be extended to the parallel read-out of multiple sensors in a sensor matrix.
For biosensors, the detection limit is an important figure of merit. The detection limit is defined as the ratio of the smallest detectable spectral shift and the sensitivity of the sensor. The latter is a measure for how much the spectrum shifts for a given change of the refractive index. There exist different types of transducers on silicon-on-insulator that use a variety of methods to achieve a low limit of detection. By using resonant sensors with high quality factors that have very narrow resonance peaks, the smallest detectable spectral shift can be minimized. Such sensors use a resonator, e.g. a ring resonator, which is exposed to a medium containing an analyte of interest. The sensors may have a surface which is adapted for the targeted analyte, e.g. which may comprise surface receptors for interacting with, e.g. temporarily or permanently binding, the target analyte. This interaction causes a local change in refractive index, which may influence the transmission spectrum of the resonator through the evanescent field, e.g. causing a wavelength offset in this spectrum.
Ring resonator sensors are known in the art, such ring resonators being made with mass fabrication compatible technology and having a detection limit as low as 7.6 10−7 RIU. Such sensors may have a bulk sensitivity of 163 nm/RIU, which is not exceptionally high. However they may accomplish a smallest detectable wavelength shift as small as 0.22 pm with an optimized sensor design and a very noise resistant optical setup and data analysis. Slot waveguides with enhanced light-matter interaction may be applied to improve the sensitivity of ring resonator sensors with a factor two to four, but increased optical losses may prevented these sensors from achieving better detection limits than normal ring resonator sensors. Integrated interferometers with large interaction lengths may also have proved to be promising, with detection limits in the order of 10−6 RIU.
Furthermore, sensors are known in the art which consist of two ring resonators, arranged in cascade such that a high sensitivity may be achievable due to the Vernier-principle. The Vernier-scale is a method to enhance the accuracy of measurement instruments. It consists of two scales with different periods, of which one slides along the other one. The overlap between measurement marks on the two scales is used to perform the measurement. This scale is commonly used in callipers and barometers, and it has also found previous application in photonic devices, e.g. in the design of integrated lasers and tunable filters.
In D. Dai, “Highly sensitive digital optical sensor based on cascaded high-Q ring-resonators”, Optics Express 2009 17 (26), such a Vernier-based sensor is disclosed. Referring to FIG. 1, such a Vernier-based sensor 1 may be implemented in Silicon-On-Insulator, for example comprising components patterned in silicon on an insulator layer 2 such as a silica layer. This sensor 1 comprises two ring resonators 3,4 with different optical roundtrip lengths, which are cascaded such that the drop signal of the first ring resonator is 3 coupled via a interconnecting waveguide 5 to the input of the second ring resonator 4, as illustrated in FIG. 1. The entire chip may be covered with a thick cladding 6, except for a region 7 in close proximity to one of the resonators, further referred to as the sensor ring resonator 4, where an opening is provided in the cladding so as to enable contacting the sensor ring resonator 4 to a test medium, for example this region 7 may be shaped such as to form a sample reservoir. This sensor ring resonator 4 will act as the sliding part of the Vernier-scale, as its evanescent field can interact with the refractive index in the environment of the sensor, where a change will cause a wavelength shift of the resonance spectrum. The other resonator, further referred to as the filter ring resonator 3, is shielded from these refractive index changes by the cladding and will act as the fixed part of the Vernier-scale. The cascade of both resonators can be designed such that a small shift of the resonance wavelengths of the sensor ring resonator will result in a much larger shift of the transmission spectrum of the cascade. Radiation may be coupled into the resonator cascade via an input waveguide 8, and collected from an output waveguide 9.
Each individual ring resonator has a comb-like transmission spectrum with peaks at its resonance wavelengths. The spectral distance between these peaks, the free spectral range, is inversely proportional to the optical roundtrip of the resonator. Therefore, each resonator in the cascade will have a different free spectral range, as illustrated by the transmission spectra of the filter ring resonator (dashed line) and of the sensor ring resonator (full line) shown in FIG. 2. As the transmission spectrum of the cascade of the two ring resonators, illustrated in FIG. 3, is the product of the transmission spectra of the individual resonators, it will only exhibit peaks at wavelengths for which two resonance peaks of the respective ring resonators at least partially overlap, and the height of each of these peaks will be determined by the amount of overlap. Thus, the cascade will have a spectral response with major peaks locating at the common resonant wavelengths of the cascaded rings.
However, this known sensor operates as a digital, i.e. a discrete, sensor, which limits the smallest detectable shift and the detection limit of the sensor. In such a discrete operating regime, the free spectral range difference between the two resonators in the cascade is large compared to the full-width at half-maximum of the resonance peaks of the individual resonators. The transmission spectrum of the cascade will then typically exhibit isolated peaks, of which the neighbouring peaks are inhibited. In such a discrete sensor, the transmission peak will hop from one filter ring resonance wavelength to another for a changing refractive index. The smallest detectable shift of the transmission spectrum of this sensor is therefore equal to the free spectral range of the filter ring resonator, which forms a limitation to the detection limit of the sensor.